Oral Care Compositions

ABSTRACT

An oral care composition comprising zinc phosphate, stannous fluoride, arginine or lysine and an organic acid buffer system, as well as methods of using the same.

FIELD

The present invention relates to an oral care composition for use in thetreatment or prevention of erosive tooth demineralization, gingivitis,plaque, and dental caries. This oral care composition includes zincphosphate, stannous fluoride, arginine or lysine, and an organic acidbuffer system.

BACKGROUND

Dental erosion involves demineralization and damage to the toothstructure due to acid attack from nonbacterial sources. Erosion is foundinitially in the enamel and, if unchecked, may proceed to the underlyingdentin. Dental erosion may be caused or exacerbated by acidic foods anddrinks, exposure to chlorinated swimming pool water, and regurgitationof gastric acids.

Dental plaque is a sticky biofilm or mass of bacteria that is commonlyfound between the teeth, along the gum line, and below the gum linemargins. Dental plaque can give rise to dental caries and periodontalproblems such as gingivitis and periodontitis. Dental caries tooth decayor tooth demineralization caused by acid produced from the bacterialdegradation of fermentable sugar.

Oral care compositions which contain stannous ion sources exhibitexcellent clinical benefits, particularly in the reduction of gingivitisand in the treatment or prevention of erosive tooth demineralization.Stannous fluoride is well known for use in clinical dentistry with ahistory of therapeutic benefits over forty years. However, untilrecently, its popularity has been limited by its instability in aqueoussolutions. The instability of stannous fluoride in water is primarilydue to the reactivity of the stannous ion (Sn²⁺). Stannous salts readilyhydrolyse above a pH of 4, resulting in precipitation from solution,with a consequent loss of the therapeutic properties.

One way to overcome the stability problems with stannous ions is tolimit the amount of water in the composition to very low levels, or touse a dual phase system. Both of these solutions to the stannous ionproblem have drawbacks. Low water oral care compositions can bedifficult to formulate with desired rheological properties, anddual-phase compositions are considerably more expensive to manufactureand package.

Soluble zinc salts, such as zinc citrate, have been used in dentifricecompositions, but have several disadvantages. Zinc ions in solutionimpart an unpleasant, astringent mouthfeel, so formulations that provideeffective levels of zinc, and also have acceptable organolepticproperties, have been difficult to achieve. Moreover, free zinc ions mayreact with fluoride ions to produce zinc fluoride, which is insolubleand so reduces the availability of both the zinc and the fluoride.Finally, the zinc ions will react with anionic surfactants such assodium lauryl sulfate, thus interfering with foaming and cleaning.

Zinc phosphate (Zn₃(PO₄)₂) is insoluble in water, although soluble inacidic or basic solutions, e.g., solutions of mineral acids, aceticacid, ammonia, or alkali hydroxides. See, e.g., Merck Index, 13^(th) Ed.(2001) p. 1812, monograph number 10205. Partly because it is viewed inthe art as a generally inert material, zinc phosphate is commonly usedin dental cements, for example in cementation of inlays, crowns,bridges, and orthodontic appliances, which are intended to endure in themouth for many years. Zinc phosphate dental cements are generallyprepared by mixing zinc oxide and magnesium oxide powders with a liquidconsisting principally of phosphoric acid, water, and buffers, so thecement comprising zinc phosphate is formed in situ by reaction withphosphoric acid.

Commercially available arginine-based toothpaste, for example, containsarginine bicarbonate and precipitated calcium carbonate, but notfluoride. The carbonate ion is believed to have cariostatic properties,and the calcium is believed to form a complex with arginine to provide aprotective effect.

The formulation of certain oral care compositions presents specialchallenges. For example, oral care compositions comprising arginine orbasic amino acids may have a basic pH, increasing potential formicrobial contamination compared to acidic formulations. Moreover, notall preservatives are active at higher pH. Some preservatives negativelyaffect the taste or aesthetics of the product. While certainpreservatives, such as ethanol or parabens, are known to be effective ata range of pHs, these preservatives are not suitable for all products orall markets.

Thus, there is a need for providing improved stannous ion containingproducts for treating or preventing erosion of tooth enamel withantimicrobial effectiveness, reducing plaque or treating or controllinggingivitis. There is also a desire for novel anti-microbial compositionsthat are stable in water and easy to manufacture.

BRIEF SUMMARY

Disclosed herein are high water oral care compositions comprising zincphosphate, stannous fluoride, arginine or lysine, and an organic acidbuffer system. Methods and uses for this composition are also describedthroughout. The compositions disclosed herein provide improvedprotection from demineralization and enhanced stannous stabilitycompared to the prior art and certain market formulations, while alsobeing able to afford the benefits derived from arginine or lysine. Insome embodiments, the zinc phosphate is added to the dentifrice as apreformed salt. In some embodiments, the organic acid buffer system is acitric acid/citrate buffer system. In some embodiments, the oral carecomposition is a toothpaste or oral gel composition.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the disclosure, are intended forpurposes of illustration only and are not intended to limit the scope ofthe disclosure.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the disclosure,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by reference in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight of the entire composition. The amounts given arebased on the active weight of the material.

It has been surprisingly found that a high water oral care compositioncomprising zinc phosphate, stannous fluoride, and an organic acid buffersystem, selected at certain concentrations and amounts, is unexpectedlymore efficacious in boosting the anti-erosion and anti-microbialproperties of a stannous ions containing formulation when compared toformulations according to the prior art.

As used herein, the term “high water” refers to an oral carecomposition, such as a toothpaste or oral gel, which comprises from 10%to 99% water, by weight of the composition. For example, the compositionmay comprise at least 10%, 15%, 20%, 25%, 30%, 35% or 40% water, up to amaximum of, for example, 60%, 70%, 80%, 90%, 95% or 99% water, by weightof the composition. As used herein, amounts of water refer to wateradded directly to the composition, as well as water added as part ofingredients or components which are added as aqueous solutions. In someembodiments, the composition comprises 10-60% water, or 10-50% water, or10-40% water, or 10-30% water, or 15-30% water, or 20-30% water, orabout 25% water, by weight of the composition.

As used herein, the term “preformed salt”—when used in reference to zincphosphate—means that the zinc phosphate is not formed in situ in theoral care composition, e.g., through the reaction of phosphoric acid andanother zinc salt.

In one aspect, the present disclosure therefore provides a high wateroral care composition (Composition 1) comprising an orally acceptablecarrier, zinc phosphate and stannous fluoride, arginine or lysine, andan organic acid buffer system. In further embodiments of this aspect,the present disclosure provides:

-   -   1.1 Composition 1, wherein the zinc phosphate is a preformed        salt of zinc phosphate (e.g., zinc phosphate hydrate).    -   1.2 Composition 1 or 1.2, wherein the zinc phosphate is present        in an amount sufficient so that the stannous fluoride        dissociates to provide a therapeutically effective amount of        stannous ions in aqueous solution.    -   1.3 Any preceding composition, wherein the amount of zinc        phosphate is from 0.05 to 10% by weight, relative to the weight        of the oral care composition, for example, from 0.1 to 8% by        weight, or from 0.5 to 5% by weight, or from 0.5 to 4% by        weight, or from 1 to 4%, or from 1 to 3% by weight, or from 2 to        3% by weight, or about 1% or about 2%, or about 2.25% or about        2.5%, by weight.    -   1.4 Any preceding composition, wherein the amount of the        stannous fluoride is from 0.01% to 5% by weight, relative to the        weight of the oral care composition, for example, from 0.05 to        4% by weight, or from 0.1% to 3% by weight, or from 0.2 to 2% by        weight, or from 0.3 to 1% by weight, or from 0.4 to 0.8% by        weight, or from 0.4 to 0.6% by weight, or from 0.4 to 0.5% by        weight, or about 0.45% by weight (e.g., 0.454% by weight).    -   1.5 Any preceding composition, wherein the amount of the water        is 10% by weight or more, relative to the weight of the oral        care composition, for example, 10-90%, or 10-80%, or 10-70%, or        10-60%, or 10-50%, or 10-40%, or 10-30%, or 15-30%, or 20-30%,        or about 18, or about 25%, by weight of the composition.    -   1.6 Any preceding composition, wherein the organic buffer system        comprises a carboxylic acid and one or more conjugate base salts        thereof, for example, alkali metal salts thereof.    -   1.7 Composition 1.6, wherein the acid is selected from citric        acid, lactic acid, malic acid, maleic acid, fumaric acid, acetic        acid, succinic acid, and tartaric acid.    -   1.8 Composition 1.6 or 1.7, wherein the one or more conjugate        base salts are independently selected from sodium and potassium        salts, or combinations thereof.    -   1.9 Composition 1.6, 1.7 or 1.8 wherein the acid is citric acid,        and the one or more conjugate base salts comprise monosodium        citrate (monobasic), disodium citrate (dibasic), trisodium        citrate (tribasic), and combinations thereof.    -   1.10 Any preceding composition, wherein the composition        comprises the organic acid buffer system in an amount of 0.1 to        5.0% by weight of the composition, measured as the combined        amount of organic acid and any conjugate base salts; for        example, from 0.5 to 4.0%, or from 1.0 to 3.0%, or from 1.5 to        3.0%, or from 1.0 to 2.4%, or from 1.0% to 2.0%, by weight of        the composition.    -   1.11 Any preceding composition, wherein the buffer system        consists of an organic acid and a conjugate base salt thereof,        for example, in a ratio of from 1:1 to 1:10, e.g., from 1:2 to        1:8, or from 1:3 to 1:6, or from 1:4 to 1:6, or from 1:5 to 1:6,        or about 1:5, by weight of the components.    -   1.12 Any preceding composition, wherein the buffer system        comprises citric acid and a sodium citrate salt (e.g., trisodium        citrate, disodium citrate, or monosodium citrate), in a ratio of        from 1:3 to 1:6, or 1:4 to 1:6, or about 1:5 (e.g., about        1:5.7), by weight.    -   1.13 Any preceding composition, wherein the oral care        composition further comprises an abrasive, for example, silica        abrasives, calcium abrasives, and other abrasives as disclosed        herein.    -   1.14 Any preceding composition, further comprising one or more        humectants, as described herein, e.g., selected from sorbitol,        glycerol, xylitol and propylene glycol, or combinations thereof.    -   1.15 Any preceding composition, further comprising one or more        surfactants, as described herein, e.g., sodium lauryl sulfate,        sodium laureth sulfate, or cocamidopropyl betaine, or        combinations thereof.    -   1.16 Any preceding composition, further comprising an effective        amount of one or more alkali phosphate salts for example        orthophosphates, pyrophosphates, tripolyphosphates,        tetraphosphates or higher polyphosphates.    -   1.17 Composition 1.16, wherein the alkali phosphate salts        comprise tetrasodium pyrophosphate or tetrapotassium        pyrophosphate, for example, in an amount of 0.5 to 5% by weight        of the composition, e.g., 1-3%, or 1-2% or about 2% by weight.    -   1.18 Composition 1.16 or 1.17, wherein the alkali phosphate        salts comprise sodium tripolyphosphate or potassium        tripolyphosphate, for example, in an amount of 0.5 to 6% by        weight of the composition, e.g., 1-4%, or 2-3% or about 3% by        weight.    -   1.19 Any preceding composition, further comprising a whitening        agent.    -   1.20 Any preceding composition, further comprising one or more        sources of zinc ions in addition to the zinc phosphate, for        example a zinc salt selected from zinc citrate, zinc oxide, zinc        lactate, zinc pyrophosphate, zinc sulfate, or zinc chloride.    -   1.21 Any preceding composition, further comprising one or more        fluoride ion sources in addition to the stannous fluoride, for        example, a fluoride ion source selected from sodium fluoride,        potassium fluoride, sodium monofluorophosphate, sodium        fluorosilicate, ammonium fluorosilicate, amine fluoride,        ammonium fluoride, and combinations thereof.    -   1.22 Any preceding composition, wherein the oral care        composition is a dentifrice, e.g., a toothpaste or oral gel.    -   1.23 Any preceding composition, wherein the pH of the        composition is from 6 to 9, such as from 6.5 to 8, or from 6.5        to 7.5, or about 7.0.    -   1.24 Any preceding composition, wherein the composition is a        single-phase composition (e.g., not a dual-phase composition).    -   1.25 Any preceding composition, wherein the composition does not        comprise one or more of zinc oxide, zinc citrate, or zinc        lactate.    -   1.26 Any preceding composition, wherein the zinc phosphate is        the only zinc ion source.    -   1.27 Any preceding composition, wherein the composition is        essentially free or free of phosphates of more than four        phosphate groups.    -   1.28 Any preceding composition, wherein the composition is        essentially free or free of phosphates of more than three        phosphate groups.    -   1.29 Any preceding composition, wherein the composition is        essentially free or free of hexametaphosphate salts (e.g.,        sodium hexametaphosphate).    -   1.30 Any preceding composition, wherein the composition is free        of methyl vinyl ether-maleic anhydride copolymer.    -   1.31 Any preceding composition, wherein the composition is free        of anionic polymer.    -   1.32 Any of the preceding compositions, wherein the composition        is effective upon application to the oral cavity, e.g., by        rinsing, optionally in conjunction with brushing, to (i) reduce        or inhibit formation of dental caries, (ii) reduce, repair or        inhibit pre-carious lesions of the enamel, e.g., as detected by        quantitative light-induced fluorescence (QLF) or electrical        caries measurement (ECM), (iii) reduce or inhibit        demineralization and promote remineralization of the teeth, (iv)        reduce hypersensitivity of the teeth, (v) reduce or inhibit        gingivitis, (vi) promote healing of sores or cuts in the        mouth, (vii) reduce levels of acid producing bacteria, (viii) to        increase relative levels of arginolytic bacteria, (ix) inhibit        microbial biofilm formation in the oral cavity, (x) raise and/or        maintain plaque pH at levels of at least pH 5.5 following sugar        challenge, (xi) reduce plaque accumulation, (xii) treat, relieve        or reduce dry mouth, (xiii) clean the teeth and oral        cavity (xiv) reduce erosion, (xv) prevents stains and/or whiten        teeth, (xvi) immunize the teeth against cariogenic bacteria;        and/or (xvii) promote systemic health, including cardiovascular        health, e.g., by reducing potential for systemic infection via        the oral tissues.    -   1.33 Any of the preceding compositions where the arginine or        lysine has the L-configuration (e.g., L-arginine).    -   1.34 Any of the preceding compositions comprising arginine in        free form.    -   1.35 Any of the preceding compositions wherein the arginine or        lysine is provided in the form of a di- or tri-peptide        comprising arginine, or salts thereof.    -   1.36 Any of the preceding compositions wherein the basic amino        acid is arginine, and wherein the arginine is present in an        amount corresponding to 1% to 15%, e.g., 3 wt. % to 10 wt. % of        the total composition weight, about e.g., 1.5%, 4%, 5%, or 8%,        wherein the weight of the basic amino acid is calculated as free        form.    -   1.37 Any of the preceding compositions wherein the amino acid is        arginine from 0.1 wt. %-6.0 wt. %. (e.g., about 1.5 wt %).    -   1.38 Any of the preceding compositions wherein the amino acid is        arginine from about 1.5 wt. %.    -   1.39 Any of the preceding compositions comprising lysine in free        form.    -   1.40 Any of the preceding compositions wherein the basic amino        acid is lysine, and wherein the lysine is present in an amount        corresponding to 1% to 15%, e.g., 3 wt. % to 10 wt. % of the        total composition weight, about e.g., 1.5%, 4%, 5%, or 8%,        wherein the weight of the basic amino acid is calculated as free        form.    -   1.41 Any of the preceding compositions wherein the amino acid is        lysine from 0.1 wt. %-6.0 wt. %. (e.g., about 1.5 wt %).    -   1.42 Any of the preceding compositions wherein the amino acid is        lysine from about 1.5 wt. %.

Any amount of zinc phosphate that is effective for protecting againstenamel erosion and/or providing any of the other benefits describedherein can be employed. Examples of suitable amounts of zinc phosphatecan range from 0.05 to 5% by weight, such as from 0.1 to 4% by weight,or from 0.5 to 3% by weight, or from 0.5 to 2% by weight, or from 0.8 to1.5% by weight, or from 0.9 to 1.1% by weight, or about 1% by weight,relative to the weight of the oral care composition.

While zinc phosphate is considered insoluble (e.g., poorly soluble), inwater, when placed in formulation, e.g., at acidic or basic pH, zincphosphate can dissolve sufficiently upon use to provide an effectiveconcentration of zinc ions to the enamel, thereby protecting againsterosion, reducing bacterial colonization and biofilm development, andproviding enhanced shine to the teeth. It has also been discovered thatzinc phosphate in a formulation with a second phosphate source enhancesphosphate deposition. As explained in WO2014/088573, the disclosure ofwhich is hereby incorporated by reference in its entirety, this is allunexpected, in view of the poor solubility of zinc phosphate, and theart-recognized view that it is substantially inert in conditions in theoral cavity, as evidenced by its widespread use in dental cement. At thesame time, the formulations containing zinc phosphate do not exhibit thepoor taste and mouthfeel, poor fluoride delivery, and poor foaming andcleaning associated with conventional zinc-based oral care products,which use more soluble zinc salts.

An amount of stannous fluoride, preferably an effective amount, isemployed in combination with the zinc phosphate in the compositions ofthe present disclosure. For example, the stannous fluoride can beemployed in an amount that is effective for providing anti-microbialbenefits, such as anti-caries protection and/or anti-gingivitisprotection, and/or anti-erosion benefits for protection of tooth enamel.Examples of suitable amounts of stannous fluoride range from 0.01% to 5%by weight, relative to the weight of the oral care composition, forexample, from 0.05 to 4% by weight, or from 0.1% to 3% by weight, orfrom 0.2 to 2% by weight, or from 0.3 to 1% by weight, or from 0.4 to0.8% by weight, or from 0.4 to 0.6% by weight, or from 0.4 to 0.5% byweight, or about 0.45% by weight (e.g., 0.454%), relative to the totalweight of the dentifrice composition. Formulations can include stannouslevels, provided by stannous fluoride, ranging for example, from 3,000ppm to 15,000 ppm (mass fraction) stannous ions in the totalcomposition. In embodiments, the soluble stannous content can range from0.1 wt % to 0.5 wt %, or more, such as from 0.15 wt % to 0.32 wt %,based on the total weight of the composition.

The combination of zinc and stannous ions provides one or more of thefollowing benefits: improved antimicrobial benefits compared to the zincions alone; improved control of plaque and/or gingivitis; improvedprotection against the erosion of tooth enamel.

In compositions comprising significant amounts of water, the zincphosphate acts as a stabilizing agent for the stannous fluoride, so thatthe stannous fluoride remains in solution in the water. As discussedabove, stannous fluoride is generally considered unstable in water dueto the hydrolytic and oxidative loss of stannous ions at typical pHranges employed in oral care compositions. Consequently, stannousfluoride is generally employed in compositions containing no water orlow water, or with a chelating agent. Tedious procedures are employed inorder to provide stable solutions in which the tendency of the stannousion to be oxidized or hydrolyzed is inhibited. Applicants havesurprisingly found that zinc phosphate and stannous fluoride can becombined together in a single phase formulation and stabilized by thepresence of an appropriate organic acid buffer system. The organic acidbuffer system helps solubilize the zinc phosphate and it helps stabilizethe soluble stannous ions.

The compositions may optionally comprise additional ingredients suitablefor use in oral care compositions. Examples of such ingredients includeactive agents, such as a fluoride source and/or a phosphate source inaddition to zinc phosphate. The compositions may be formulated in asuitable dentifrice base, e.g., comprising abrasives, e.g., silicaabrasives, surfactants, foaming agents, vitamins, polymers, enzymes,humectants, thickeners, additional antimicrobial agents, preservatives,flavorings, colorings, and/or combinations thereof. Examples of suitabledentifrice bases are known in the art. Alternatively, the compositionsmay be formulated as a gel (e.g., for use in a tray), chewing gum,lozenge or mint. Examples of suitable additional ingredients that can beemployed in the compositions of the present disclosure are discussed inmore detail below.

Active Agents:

The compositions of the disclosure may comprise various other agentsthat are active to protect and enhance the strength and integrity of theenamel and tooth structure and/or to reduce bacteria and associatedtooth decay and/or gum disease or to provide other desired benefits.Effective concentration of the active ingredients used herein willdepend on the particular agent and the delivery system used. Theconcentration will also depend on the exact salt or polymer selected.For example, where the active agent is provided in salt form, thecounterion will affect the weight of the salt, so that if the counterionis heavier, more salt by weight will be required to provide the sameconcentration of active ion in the final product.

Compositions of the disclosure may contain from 0.1 to 1 wt % of anantibacterial agent, such as about 0.3 wt. %. Any suitable antimicrobialactives can be employed.

Basic Amino Acids

The basic amino acids which can be used in the compositions and methodsof the invention include not only naturally occurring basic amino acids,such as arginine, lysine, and histidine, but also any basic amino acidshaving a carboxyl group and an amino group in the molecule, which arewater-soluble and provide an aqueous solution with a pH of 7 or greater.

Accordingly, basic amino acids include, but are not limited to,arginine, lysine, serine, citrullene, ornithine, creatine, histidine,diaminobutanoic acid, diaminoproprionic acid, salts thereof orcombinations thereof. In a particular embodiment, the basic amino acidsare selected from arginine, citrullene, and ornithine.

In certain embodiments, the basic amino acid is arginine or lysine, forexample, L-arginine, or a salt thereof.

The compositions of the invention are intended for topical use in themouth and so salts for use in the present invention should be safe forsuch use, in the amounts and concentrations provided. Suitable saltsinclude salts known in the art to be pharmaceutically acceptable saltsare generally considered to be physiologically acceptable in the amountsand concentrations provided. Physiologically acceptable salts includethose derived from pharmaceutically acceptable inorganic or organicacids or bases, for example acid addition salts formed by acids whichform a physiological acceptable anion, e.g., hydrochloride or bromidesalt, and base addition salts formed by bases which form aphysiologically acceptable cation, for example those derived from alkalimetals such as potassium and sodium or alkaline earth metals such ascalcium and magnesium. Physiologically acceptable salts may be obtainedusing standard procedures known in the art, for example, by reacting asufficiently basic compound such as an amine with a suitable acidaffording a physiologically acceptable anion.

Fluoride Ion Source:

The oral care compositions can include one or more additional fluorideion sources, e.g., soluble fluoride salts. A wide variety of fluorideion-yielding materials can be employed as sources of soluble fluoride inthe present compositions. Examples of suitable fluoride ion-yieldingmaterials are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S.Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,to Widder et al, the disclosure of each of which is hereby incorporatedby reference in their entirety. Representative fluoride ion sourcesinclude, but are not limited to, sodium fluoride, potassium fluoride,sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride, and combinationsthereof. In certain embodiments the fluoride ion source includes sodiumfluoride, sodium monofluorophosphate as well as mixtures thereof. Incertain embodiments, the oral care composition of the disclosure maycontain stannous fluoride and any additional source of fluoride ions orfluorine-providing agents in amounts sufficient to supply, in total,from 25 ppm to 25,000 ppm (mass fraction) of fluoride ions, generally atleast 500 ppm, e.g., from 500 to 2000 ppm, e.g., from 1000 to 1600 ppm,e.g., about 1450 ppm. The appropriate level of fluoride will depend onthe particular application. A toothpaste for general consumer use wouldtypically have from 1000 to about 1500 ppm, with pediatric toothpastehaving somewhat less. A dentifrice or coating for professionalapplication could have as much as 5,000 or even about 25,000 ppmfluoride. Additional fluoride ion sources may be added to thecompositions of the disclosure at a level of from 0.01 wt. % to 10 wt. %in one embodiment or from 0.03 wt. % to 5 wt. %, and in anotherembodiment from 0.1 wt. % to 1 wt. % by weight of the composition. Asdiscussed above, weights of fluoride salts to provide the appropriatelevel of fluoride ion will vary based on the weight of the counterion inthe salt.

Abrasives:

The compositions of the disclosure can include abrasives. Examples ofsuitable abrasives include silica abrasives, such as standard cleaningsilicas, high cleaning silicas or any other suitable abrasive silicas.Additional examples of abrasives that can be used in addition to or inplace of the silica abrasives include, for example, a calcium phosphateabrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂), hydroxyapatite(Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate (CaHPO₄.2H₂O, alsosometimes referred to herein as DiCal) or calcium pyrophosphate; calciumcarbonate abrasive; or abrasives such as sodium metaphosphate, potassiummetaphosphate, aluminum silicate, calcined alumina, bentonite or othersiliceous materials, or combinations thereof.

Silica abrasive polishing materials useful herein, as well as the otherabrasives, generally have an average particle size ranging between 0.1and 30 microns, such as between 5 and 15 microns. The silica abrasivescan be from precipitated silica or silica gels, such as the silicaxerogels described in U.S. Pat. No. 3,538,230, to Pader et al. and U.S.Pat. No. 3,862,307, to Digiulio, the disclosures of which areincorporated herein by reference in their entireties. Particular silicaxerogels are marketed under the trade name Syloid® by the W. R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J. M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 115 and119. These silica abrasives are described in U.S. Pat. No. 4,340,583, toWason, the disclosure of which is incorporated herein by reference inits entirety. In certain embodiments, abrasive materials useful in thepractice of the oral care compositions in accordance with the disclosureinclude silica gels and precipitated amorphous silica having an oilabsorption value of less than 100 cc/100 g silica, such as from 45cc/100 g to 70 cc/100 g silica. Oil absorption values are measured usingthe ASTA Rub-Out Method D281. In certain embodiments, the silicas arecolloidal particles having an average particle size of from 3 microns to12 microns, and from 5 to 10 microns. Examples of low oil absorptionsilica abrasives useful in the practice of the disclosure are marketedunder the trade designation Sylodent XWA® by Davison Chemical Divisionof W.R. Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silicahydrogel composed of particles of colloidal silica having a watercontent of 29% by weight averaging from 7 to 10 microns in diameter, andan oil absorption of less than 70 cc/100 g of silica is an example of alow oil absorption silica abrasive useful in the practice of the presentdisclosure.

Any suitable amount of silica abrasive can be employed. Examples ofsuitable amounts include 10 wt. % or more dry weight of silicaparticles, such as from 15 wt. % to 30 wt. % or from 15 wt. % to 25 wt.%, based on the total weight of the composition.

Foaming Agents:

The oral care compositions of the disclosure also may include an agentto increase the amount of foam that is produced when the oral cavity isbrushed. Illustrative examples of agents that increase the amount offoam include, but are not limited to polyoxyethylene and certainpolymers including, but not limited to, alginate polymers. Thepolyoxyethylene may increase the amount of foam and the thickness of thefoam generated by the oral care compositions of the present disclosure.Polyoxyethylene is also commonly known as polyethylene glycol (“PEG”) orpolyethylene oxide. The polyoxyethylenes suitable for compositions ofthe present disclosure may have a molecular weight of from 200,000 to7,000,000. In one embodiment the molecular weight may be from 600,000 to2,000,000 and in another embodiment from 800,000 to 1,000,000. Polyox®is the trade name for the high molecular weight polyoxyethylene producedby Union Carbide. The foaming agent, (e.g., polyoxyethylene) may bepresent in an amount of from 0.1% to 50%, in one embodiment from 0.5% to20% and in another embodiment from 1% to 10%, or from 2% to 5% by weightof the oral care compositions of the present disclosure.

Surfactants:

The compositions useful in the compositions of the present disclosuremay contain anionic surfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂₀SO₃Na),    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate),    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In certain embodiments,the anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 10 to 18 carbon atoms in the alkyl radicaland the water-soluble salts of sulfonated monoglycerides of fatty acidshaving from 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroylsarcosinate and sodium coconut monoglyceride sulfonates are examples ofanionic surfactants of this type. In particular embodiments, the anionicsurfactant is selected from sodium lauryl sulfate and sodium etherlauryl sulfate. In a particular embodiment, the compositions of thedisclosure comprise sodium lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. In one embodiment,the anionic surfactant is present in a toothpaste at from 0.3% to 4.5%by weight, e.g., about 1.5%. The compositions of the disclosure mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, suitable surfactants are thosewhich are reasonably stable throughout a wide pH range. Surfactants aredescribed more fully, for example, in U.S. Pat. No. 3,959,458, toAgricola et al.; U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No.4,051,234, to Gieske et al, the disclosures of which are incorporatedherein by reference in their entireties.

The surfactant or mixtures of compatible surfactants that are includedin addition to the anionic surfactants can be present in thecompositions of the present disclosure in from 0.1% to 5.0%, in anotherembodiment from 0.3% to 3.0% and in another embodiment from 0.5% to 2.0%by weight of the total composition. These ranges do not include theanionic surfactant amounts.

In some embodiments, the compositions of the present disclosure includea zwitterionic surfactant, for example a betaine surfactant, for examplecocamidopropylbetaine, e.g. in an amount of from 0.1% to 4.5% by weight,e.g. from 0.5 to 2% by weight cocamidopropylbetaine.

Tartar Control Agents:

In various embodiments of the present disclosure, the compositionscomprise an anticalculus (tartar control) agent. Suitable anticalculusagents include, without limitation, phosphates and polyphosphates (forexample pyrophosphates and tripolyphosphates), polyaminopropanesulfonicacid (AMPS), hexametaphosphate salts, zinc citrate trihydrate,polypeptides, polyolefin sulfonates, polyolefin phosphates, anddiphosphonates. The compositions of the disclosure thus may comprisephosphate salts in addition to the zinc phosphate. In particularembodiments, these salts are alkali phosphate salts, e.g., salts ofalkali metal hydroxides or alkaline earth hydroxides, for example,sodium, potassium or calcium salts. “Phosphate” as used hereinencompasses orally acceptable mono- and polyphosphates, for example,P₁₋₆ phosphates, for example monomeric phosphates such as monobasic,dibasic or tribasic phosphate; and dimeric phosphates such aspyrophosphates; and multimeric phosphates, such as tripolyphosphates,tetraphosphates, hexaphosphates and hexametaphosphates (e.g., sodiumhexametaphosphate). In particular examples, the selected phosphate isselected from alkali dibasic phosphate and alkali pyrophosphate salts,e.g., selected from sodium phosphate dibasic, potassium phosphatedibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodiumtripolyphosphate, and mixtures of any of two or more of these. In aparticular embodiment, for example the compositions may comprisetetrasodium pyrophosphate in an amount of from 0.5 to 5% by weight,e.g., 1-3%, or 1-2% or about 2% by weight of the composition. In anotherembodiment, the compositions may comprise a mixture of tetrasodiumpyrophosphate (TSPP) and sodium tripolyphosphate (STPP), e.g., inproportions of TSPP at from 0.5 to 5 wt. %, such as from 1 to 2 wt. %and STPP at from 0.5% to 6 wt. %, such as 1 to 4%, or 2 to 3% by weightof the composition. Such phosphates are provided in an amount effectiveto reduce erosion of the enamel, to aid in cleaning the teeth, and/or toreduce tartar buildup on the teeth, for example in an amount of from 0.2to 20 wt. %, e.g., from 1 to 15 wt. %, by weight of the composition.

Flavoring Agents:

The oral care compositions of the disclosure may also include aflavoring agent. Flavoring agents which are used in the practice of thepresent disclosure include, but are not limited to, essential oils aswell as various flavoring aldehydes, esters, alcohols, and similarmaterials. Examples of the essential oils include oils of spearmint,peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram,cinnamon, lemon, lime, grapefruit, and orange. Also useful are suchchemicals as menthol, carvone, and anethole. Certain embodiments employthe oils of peppermint and spearmint. The flavoring agent may beincorporated in the oral composition at a concentration of from 0.1 to5% by weight e.g., from 0.5 to 1.5% by weight.

Polymers:

The oral care compositions of the disclosure may also include additionalpolymers to adjust the viscosity of the formulation or enhance thesolubility of other ingredients. Such additional polymers includepolyethylene glycols, polysaccharides (e.g., cellulose derivatives, forexample carboxymethyl cellulose, hydroxymethyl cellulose, ethylcellylose, microcrystalline cellulose or polysaccharide gums, forexample xanthan gum, guar gum or carrageenan gum). Acidic polymers, forexample polyacrylate gels, may be provided in the form of their freeacids or partially or fully neutralized water soluble alkali metal(e.g., potassium and sodium) or ammonium salts. In one embodiment, theoral care composition may contain PVP. PVP generally refers to a polymercontaining vinylpyrrolidone (also referred to as N-vinylpyrrolidone,N-vinyl-2-pyrrolidione and N-vinyl-2-pyrrolidinone) as a monomeric unit.The monomeric unit consists of a polar imide group, four non-polarmethylene groups and a non-polar methane group.

In some embodiments, the compositions of the disclosure comprise one ormore polyethylene glycols, for example, polyethylene glycols in amolecular weight range from 200 to 800. For example, the compositionsmay comprise one or more of polyethylene glycol 200, polyethylene glycol300, polyethylene glycol 400, polyethylene glycol, 600 or polyethyleneglycol 800.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of from 0.5% to5.0% by weight of the total composition are used.

In some embodiments, the compositions of the disclosure may include ananionic polymer, for example in an amount of from 0.05 to 5%. Examplesof such agents generally known for use in dentifrice are disclosed inU.S. Pat. Nos. 5,188,821 and 5,192,531, both of which are incorporatedherein by reference in their entirety; and include synthetic anionicpolymeric polycarboxylates, such as 1:4 to 4:1 copolymers of maleicanhydride or acid with another polymerizable ethylenically unsaturatedmonomer, preferably methyl vinyl ether/maleic anhydride having amolecular weight (M.W.) of from 30,000 to 1,000,000, such as from300,000 to 800,000. These copolymers are available for example asGantrez, e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) andpreferably S-97 Pharmaceutical Grade (M.W. 700,000) available from ISPTechnologies, Inc., Bound Brook, N.J. 08805. The enhancing agents whenpresent are present in amounts ranging from 0.05 to 3% by weight. Otheroperative polymers include those such as the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Suitable generally, are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility. Afurther class of polymeric agents includes a composition containinghomopolymers of substituted acrylamides and/or homopolymers ofunsaturated sulfonic acids and salts thereof, in particular wherepolymers are based on unsaturated sulfonic acids selected fromacrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropanesulfonic acid having a molecular weight of from 1,000 to 2,000,000.Another useful class of polymeric agents includes polyamino acidscontaining proportions of anionic surface-active amino acids such asaspartic acid, glutamic acid and phosphoserine, e.g. as disclosed inU.S. Pat. No. 4,866,161, issued to Sikes et al., which is alsoincorporated herein by reference in its entirety.

In some embodiments, there are no anionic polymers present in thecomposition. In other embodiments, there may be anionic polymerspresent, but they do not include copolymers of methyl vinyl ether andmaleic acid or anhydride.

Humectants:

Within certain embodiments of the oral compositions, it is alsodesirable to incorporate a humectant to prevent the composition fromhardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerin,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the disclosure, theprincipal humectant is one of glycerin, sorbitol or a combinationthereof. The humectant may be present at levels of greater than 15 wt.%, such as from 15 wt. % to 55 wt. %, or from 20 wt. % to 50 wt. %, orfrom 20 wt. % to 40 wt. %, or about 20% or about 30% or about 40%, basedon the total weight of the composition.

Other Optional Ingredients:

In addition to the above-described components, the embodiments of thisdisclosure can contain a variety of optional oral care ingredients someof which are described below. Optional ingredients include, for example,but are not limited to, adhesives, sudsing agents, flavoring agents,sweetening agents such as sodium saccharin, additional antiplaqueagents, abrasives, aesthetics such as TiO₂ coated mica or other coloringagents, such as dyes and/or pigments.

In some embodiments, the compositions of the present disclosure can haveany pH suitable for in a product for use in oral care. Examples ofsuitable pH ranges are from 6 to 9, such as from 6.5 to 8, or 6.5 to7.5, or about 7.0.

In some embodiments, the oral care compositions of the presentdisclosure are either essentially free of, free of, or do not includeany sodium hexametaphosphate. In some embodiments, the oral carecompositions of the present disclosure are either essentially free of,free of, or do not include any halogenated diphenyl ethers (e.g.,triclosan).

By “essentially free” is meant that the compositions have no more than0.01% by weight of these compounds.

In some embodiments, the compositions of the present disclosure areeither essentially free of, free of or do not include any complexingagents for increasing solubility of zinc phosphate and/or formaintaining the stannous fluoride in solution. Examples of knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include the chelating agents taught in U.S. PatentApplication No. 2007/0025928, the disclosure of which is herebyincorporated by reference in its entirety. Such chelating agents includemineral surface-active agents, including mineral surface-active agentsthat are polymeric and/or polyelectrolytes and that are selected fromphosphorylated polymers, wherein if the phosphorylated polymer is apolyphosphate, the polyphosphate has average chain length of 3.5 ormore, such as 4 or more; polyphosphonates; polycarboxylates;carboxy-substituted polymers; copolymers of phosphate- orphosphonate-containing monomers or polymers with ethylenicallyunsaturated monomers, amino acids, proteins, polypeptides,polysaccharides, poly(acrylate), poly(acrylamide), poly(methacrylate),poly(ethacrylate), poly(hydroxyalkylmethacrylate), poly(vinyl alcohol),poly(maleic anhydride), poly(maleate) poly(amide), poly(ethylene amine),poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) andpoly(vinyl benzyl chloride); and mixtures thereof. Other knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include those taught in CA 2634758, the disclosure ofwhich is incorporated here by reference in its entirety. Examplesinclude polyphosphorylated inositol compounds such as phytic acid,myo-inositol pentakis(dihydrogen phosphate); myo-inositoltetrakis(dihydrogen phosphate), myo-inositol trikis(dihydrogenphosphate), and alkali metal, alkaline earth metal or ammonium salts ofany of the above inositol compounds. Phytic acid is also known asmyo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositolhexaphosphoric acid.

In another aspect, the present disclosure provides a method of treatmentor prevention of erosive tooth demineralization, gingivitis, plaque,and/or dental caries, the method comprising the application to the oralcavity of a person in need thereof a composition according to theinvention (e.g., Composition 1.0 et seq), e.g., by brushing, forexample, one or more times per day.

In another aspect, the present disclosure provides a method of using thecompositions described herein (e.g., any of Compositions 1.0 et seq) toincrease zinc levels in the enamel and to treat, reduce or control theincidence of enamel erosion. The methods comprise applying any of thecompositions as described herein to the teeth, e.g., by brushing, orotherwise administering the compositions to the oral cavity of a subjectin need thereof. The compositions can be administered regularly, suchas, for example, one or more times per day. In various embodiments,administering the compositions of the present disclosure to a patientcan provide one or more of the following benefits: (i) reducehypersensitivity of the teeth, (ii) reduce plaque accumulation, (iii)reduce or inhibit demineralization and promote remineralization of theteeth, (iv) inhibit microbial biofilm formation in the oral cavity, (v)reduce or inhibit gingivitis, (vi) promote healing of sores or cuts inthe mouth, (vii) reduce levels of acid producing bacteria, (viii)increase relative levels of non-cariogenic and/or non-plaque formingbacteria, (ix) reduce or inhibit formation of dental caries, (x) reduce,repair or inhibit pre-carious lesions of the enamel, e.g., as detectedby quantitative light-induced fluorescence (QLF) or electrical cariesmeasurement (ECM), (xi) treat, relieve or reduce dry mouth, (xii) cleanthe teeth and oral cavity, (xiii) reduce erosion, (xiv) whiten teeth;(xv) reduce tartar build-up, and/or (xvi) promote systemic health,including cardiovascular health, e.g., by reducing potential forsystemic infection via the oral tissues. The disclosure further providescompositions for use in any of the above methods. Further embodimentsprovide methods wherein at least one tooth is remineralized afteradministration of a composition as described herein.

The present application further discloses a method of making any of thecompositions of the present disclosure. The method comprises combiningzinc phosphate and stannous fluoride in water to form an aqueous zincphosphate mixture. In some embodiments, the zinc phosphate is added tothe dentifrice composition as a preformed salt and remains essentiallyinsoluble in the aqueous mixture. The amount of water employed in themixture can be any of the amounts recited herein for the compositions ofthe present disclosure. Any standard mixing techniques can be employedto combine the ingredients and form a stable composition without theneed for additional complexing agents to solubilize the stannousfluoride, such as any of the above disclosed complexing or chelatingagents, or the use of anhydrous mixing techniques such as dissolvingstannous fluoride in an anhydrous material such as glycerin.

EXAMPLES

Examples 1 and 2 below look at the amount of water soluble zinc andstannous using flame atomic absorption spectrophotometry (FAAS). Allsamples (F, Sn, and Zn) are diluted in water, initially, and thensubject to accelerated aging over the course of 13 weeks, at either 25°C. or 40° C. This method is based on the principle that water soluble Zncan be measured in oral care products by FAAS after dilution of samplein water. With respect to Sn, a portion of oral care product is digestedwith an acid mixture (acid soluble tin) or dispersed with water (watersoluble tin). Solutions are transferred to a volumetric flask, dilutedto volume with water and centrifuged. Tin is detected in the supernatantby atomic absorption spectroscopy and quantitated by comparing theabsorbance of the sample solution to absorbances of external calibrationstandards of known tin concentration.

Additionally, Examples 1 and 2 below use gradient elution ionchromatograph, incorporating conductivity detection, to assay fluoride.Samples are prepared as aqueous slurries followed by centrifugation anddilution. The working solutions are analyzed by gradient ionchromatography with suppressed conductivity detection. Analyteconcentrations are determined by relating the component peak areas tocorresponding areas of external calibration standards.

Example 1: Stannous Stability with Arginine and Citrate Buffer

(*ZnP is meant to denote Zinc Phosphate throughout the specification andexamples)

TABLE 1 F 13 Wk* Sn 13 wk* Zn 13 Wk* F (25° C., Sn (25° C., Zn (25° C.,(Initial) 40° C.) (Initial) 40° C.) (Initial) 40° C.) (ppm) (ppm) % sol% sol % sol % sol SnF, + ZnP + 1127  1136, 1111 0.14 0.05, 0.05 0.280.26 Arg 0.26 SnF, + ZnP + 1196 1068, 969 0.2 0.18, 0.15 0.31 0.25 1.2Buffer 0.21 SnF, + ZnP + 1134 1063, 967 0.18 0.11, 0.10 0.27 0.31 Arg +1.2 Buffer 0.27 (Composition A) SnF, + ZnP + 1141  1067, 1011 0.23 0.15,0.13 0.34 0.43 Arg + 2.4Buffer 0.23 (Composition B) SnF, + ZnP+ 11971069, 963 0.26  0.2, 0.17 0.38 0.51 Arg + 3.6 Buffer 0.47 (CompositionC) *Values at 13 weeks listed on top are aged at 25° C., values at 13weeks listed on the bottom are aged at 40° C.

The citrate buffer was tested for its ability to stabilize stannous ionsin combination with arginine. Ion concentration was measured over thecourse of 13 weeks. Formulations with the organic acid buffer systemretained a higher percentage of stannous ions than the comparativeformulation which did not comprise the organic acid buffer system. Theorganic acid buffer described above in Compositions A-C containstrisodium citrate dihydrate and citric acid in combination witharginine. Amounts of the buffer are listed as a percentage by weight ofthe composition.

Formulations with SnZp and Arginine (w/o any citrate buffer) retainedonly about 36% of the original stannous ion concentration by week 13.Corresponding formulations that contain SnZp, Arginine, and Buffer(1.2%, 2.4%, and 3.6%) were able to retain much more of the originalstannous concentration at room temperature ((25 C)): about 61% (at 1.2%buffer), about 65% (at 2.4% buffer) and about 65% (at 3.6% buffer).

Example 2: Stannous Stability with Lysine and Citrate Buffer

TABLE 2 Initial Initial Initial Aged % Aging Time % Sol. Aged % % Sol.Aged % % F Sol. F Description pt Tin Sol. Tin Zn Sol. Zinc (ppm) (ppm)SnF + 2.35% Initial 25 C 0.25 0.21 1112 ZnP, 1.5% Lysine 1.2% Buffer(Composition D) 4 wks(25 C/ 0.17/0.14 0.25/0.24 1106/1064 40 C) 8 wks(25 C/ 0.19/0.17 0.27/0.25 1059/986 40 C) 13 wks (25 C/ 0.15/0.130.25/0.24 40 C) SnF + 2.35% 0.21 0.26 1081 ZnP, 1.5% Lysine 2.4.% Buffer(Composition E) 4 wks(25 0.23/0.20 0.36/0.34 1098/1027 C/40 C) 8 wks0.28/0.25 0.41/0.31 1033/938 13 wks 0.21/0.18 0.35/0.34 SnF + 2.35% 0.30.48 1056 ZnP, 1.5% Lysine, 3.6% Buffer (Composition F) 4 wks(250.31/0.26 0.49/0.41 1066/1002 C/40 C) 8 wks 0.32/0.29 0.42/0.48 1048/90613 wks 0.26/0.24 0.47/0.44

The citrate buffer was tested for its ability to stabilize stannous ionsin combination with lysine. Ion concentration was measured over thecourse of 13 weeks. The organic acid buffer described above inCompositions D-F contains trisodium citrate dihydrate and citric acid incombination with arginine. Amounts of the buffer are listed as apercentage by weight of the composition.

Example 3: Zinc Uptake in Bovine Teeth Assays

The three dentifrice composition shown above were compared in a stannousand zinc ion uptake experiments using bovine enamel.

Metal ion uptake is measured using the ESCA technique (X-rayphotoelectron spectroscopy). Bovine enamel specimens are used to prepare3 mm wide disks of bovine enamel in which all but the exposed enamelsurface is protected with acrylic resin. Each enamel sample is etchedwith 1M perchloric acid solution, and then rinsed. 2 mL of fresh humansaliva is then added, and the samples are incubated at 37° C. for 2hours in order to cause pellicle formation. After removing the salivaand rinsing, the samples are treated with 2 mL of a 1:2 slurry of testcomposition in distilled water for 2 minutes at 37° C. with shaking. Onesample is treated with water as a negative control to determine baselinemetal ion content. After rinsing the samples with water, they aresubmitted to ESCA analysis. The baseline metal ion levels measured inthe negative control are subtracted from the other test measurements todetermine metal ion uptake from the dentifrice compositions. The resultsare shown in Table 3 below.

Test Formulations with Dentifrice Formulation:

-   -   Test Formulation A: SnF+2.35% ZnP, 1.5% Lysine, 1.2% Buffer    -   Test Formulation B: SnF+2.35% ZnP, 1.5% Lysine, 2.4% Buffer    -   Test Formulation C: SnF+2.35% ZnP, 1.5% Lysine, 3.6% Buffer    -   Control Formulations contain: 0.454% SnF, and 2.5% zinc lactate.        The results demonstrate improved metal deposition of zinc, in in        vitro bovine uptake assays when compared to control formulations        which contain 0.454% SnF and 2.5% zinc lactate, but which do not        contain zinc phosphate:

TABLE 3 Relative Increase in Metal Deposition: Zinc (ppm)* TestFormulation A 1.7 Test Formulation B 2.0 Test Formulation C 2.1 ControlFormulation 1 *Values are normalized to control and show increase ofzinc deposition relative to control

Table 4 demonstrates the buffer composition used in above Examples 1-3.

TABLE 4 Buffer System (wt %) Test Comp. Sodium Citrate* Citric Acid TestCompositions w/o Buffer 0.00 0.00 Compositions with 1.2% Buffer 1.0 0.2Compositions with 2.4% Buffer 2.0 0.4 Compositions with 3.6% Buffer 3.00.6

The water concentration of the above formulations is between 17.0% to21.0% by wt. These are considered “high water” formulations. Therefore,the Applicants have addressed the instability of stannous ions withouthaving to resort to either a.) low water formulations; or b.) dual phasecompositions.

Experimental dentifrice compositions used to observe stannous ionstability are prepared based on the base formulation shown in Tables 5and 6. Each dentifrice comprises 0.454% stannous fluoride and 2.35% zincphosphate hydrate, and arginine 1.5%, but varies in the concentration ofcitric acid and trisodium citrate dihydrate present—these concentrationsare detailed in the above Table 2.

Ingredients of Representative Formulas in Tables 5 and 6 are listed byweight of the composition.

TABLE 5 Ingredient Weight % Water Q.S. Humectants (Sorbitol, Glycerin,Propylene Glycol, 40-47  Polyethylene Glycol) Abrasives 20 Thickeners3.6 Trisodium Citrate, Dihydrate 0.0-3.0 Zinc Phosphate 2.35 Flavor,Sweetener, Colors 0.65 Tetrasodium Pyrophosphate 2 Anionic Surfactant1.5 Microcrystalline Cellulose/Sodium CMC NF 0.5-1.5 ZwitterionicSurfactant 1.25 Citric Acid- Anhydrous 0.0-3.0 Stannous Fluoride 0.454Arginine 1.50%  TOTAL 100%

TABLE 6 Ingredient Weight % Water Q.S. Humectants (Sorbitol, Glycerin,Propylene Glycol, 40-47  Polyethylene Glycol) Abrasives 20 Thickeners3.6 Trisodium Citrate, Dihydrate 0.0-3.0 Zinc Phosphate 2.35 Flavor,Sweetener, Colors 0.65 Tetrasodium Pyrophosphate 2 Anionic Surfactant1.5 Microcrystalline Cellulose/Sodium CMC NF  .5-1.5 ZwitterionicSurfactant 1.25 Citric Acid-Anhydrous 0.0-3.0 Stannous Fluoride 0.454Lysine 1.50%  TOTAL 100%

While the present invention has been described with reference toembodiments, it will be understood by those skilled in the art thatvarious modifications and variations may be made therein withoutdeparting from the scope of the present invention as defined by theappended claims.

1. A high water oral care composition comprising an orally acceptablecarrier, zinc phosphate, stannous fluoride, arginine or lysine, and anorganic acid buffer system.
 2. A composition according to claim 1,wherein the zinc phosphate is a preformed salt of zinc phosphate.
 3. Acomposition according to claim 1, wherein the amount of zinc phosphateis present in an amount of from 0.05 to 10% by weight, relative to theweight of the oral care composition.
 4. A composition according to claim1, wherein the amount of the stannous fluoride is from 0.01% to 5% byweight, relative to the weight of the oral care composition.
 5. Acomposition according to claim 1, wherein the amount of the water is 10%by weight or more, relative to the weight of the oral care composition.6. A composition according claim 1, wherein the organic buffer systemcomprises a carboxylic acid and one or more conjugate base saltsthereof, for example, alkali metal salts thereof.
 7. A compositionaccording to claim 6, wherein the acid is selected from citric acid,lactic acid, malic acid, maleic acid, fumaric acid, acetic acid,succinic acid, and tartaric acid.
 8. A composition according to claim 6,wherein the one or more conjugate base salts are independently selectedfrom sodium and potassium salts, or combinations thereof.
 9. Acomposition according to claim 6, wherein the acid is citric acid, andthe one or more conjugate base salts comprise monosodium citrate(monobasic), disodium citrate (dibasic), trisodium citrate (tribasic),and combinations thereof.
 10. A composition according to claim 1,wherein the composition comprises the organic acid buffer system in anamount of 0.1 to 5.0% by weight of the composition, measured as thecombined amount of organic acid and any conjugate base salt.
 11. Acomposition according to claim 1, wherein the buffer system comprisescitric acid and a sodium citrate salt, in a ratio of from 1:3 to 1:6.12. A composition according to claim 1, wherein the compositioncomprises arginine or lysine at about 1.5% by wt.
 13. A compositionaccording to claim 1, wherein the composition comprises arginine.
 14. Acomposition according to claim 1, wherein the composition compriseslysine.
 15. (canceled)
 16. (canceled)
 17. A composition according toclaim 1, further comprising an effective amount of one or more alkaliphosphate salts.
 18. A composition according to claim 17, wherein thealkali phosphate salts comprise tetrasodium pyrophosphate ortetrapotassium pyrophosphate, optionally in an amount of 0.5 to 5% byweight of the composition.
 19. A composition according to claim 17,wherein the alkali phosphate salts comprise sodium tripolyphosphate orpotassium tripolyphosphate, optionally in an amount of 0.5 to 6% byweight of the composition.
 20. A composition according to claim 1,further comprising one or more sources of zinc ions in addition to thezinc phosphate, for example, a zinc salt selected from zinc citrate,zinc oxide, zinc lactate, zinc pyrophosphate, zinc sulfate, or zincchloride.
 21. A composition according to claim 1, wherein the oral carecomposition is a dentifrice.
 22. A method of treatment or prevention oferosive tooth demineralization, gingivitis, plaque, and/or dentalcaries, the method comprising the application to the oral cavity of aperson in need thereof a composition according to claim
 1. 23.(canceled)